Stochastic growth and selective stabilization generate stereotyped dendritic arbors.

Stereotyped dendritic arbors are shaped by dynamic and stochastic growth during neuronal development. It remains unclear how guidance receptors and ligands coordinate branch dynamic growth, retraction, and stabilization to specify dendritic arbors. We previously showed that extracellular ligand SAX-7/LICAM dictates the shape of the PVD sensory neuron via binding to the dendritic guidance receptor DMA-1, a single transmembrane adhesion molecule. Here, we perform structure-function analyses of DMA-1 and unexpectedly find that robust, stochastic dendritic growth does not require ligand-binding. Instead, ligand-binding inhibits growth, prevents retraction, and specifies arbor shape. Furthermore, we demonstrate that dendritic growth requires a pool of ligand-free DMA-1, which is maintained by receptor endocytosis and reinsertion to the plasma membrane via recycling endosomes. Mutants defective of DMA-1 endocytosis show severely truncated dendritic arbors. We present a model in which ligand-free guidance receptor mediates intrinsic, stochastic dendritic growth, while extracellular ligands instruct dendrite shape by inhibiting growth.

Association of Neighborhood Socioeconomic Deprivation With Utilization and Costs of Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: A retrospective analysis. OBJECTIVE: The aim of our study was to analyze the association of Area Deprivation Index (ADI) with the utilization and costs of elective anterior cervical discectomy and fusion (ACDF) surgery. SUMMARY OF BACKGROUND DATA: ADI, a comprehensive neighborhood-level measure of socioeconomic disadvantage, has been shown to be associated with worse perioperative outcomes in a variety of surgical settings. MATERIALS AND METHODS: The Maryland Health Services Cost Review Commission Database was queried to identify patients who underwent primary elective ACDF between 2013 and 2020 in the state. Patients were stratified into tertiles by ADI, from least disadvantaged (ADI1) to most disadvantaged (ADI3). The primary endpoints were ACDF utilization rates per 100,000 adults and episode-of-care total costs. Univariable and multivariable regression analyses were performed. RESULTS: A total of 13,362 patients (4984 inpatient and 8378 outpatient) underwent primary ACDF during the study period. In our study, there were 2,401 (17.97%) patients residing in ADI1 neighborhoods (least deprived), 5974 (44.71%) in ADI2, and 4987 (37.32%) in ADI3 (most deprived). Factors associated with increased surgical utilization were increasing ADI, outpatient surgical setting, non-Hispanic ethnicity, current tobacco use, and diagnoses of obesity and gastroesophageal reflux disease. Factors associated with lower surgical utilization were: non-white race, rurality, Medicare/Medicaid insurance status, and diagnoses of cervical disk herniation or myelopathy. Factors associated with higher costs of care were increasing ADI, older age, Black/African American race, Medicare or Medicaid insurance, former tobacco use, and diagnoses of ischemic heart disease and cervical myelopathy. Factors associated with lower costs of care were outpatient surgical setting, female sex, and diagnoses of gastroesophageal reflux disease and cervical disk herniation. CONCLUSIONS: Neighborhood socioeconomic deprivation is associated with increased episode-of-care costs in patients undergoing ACDF surgery. Interestingly, we found greater utilization of ACDF surgery among patients with higher ADI. LEVEL OF EVIDENCE: 3.

Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum.

Animals encounter microorganisms in their habitats, adapting physiology and behavior accordingly. The nematode Caenorhabditis elegans is found in microbe-rich environments; however, its responses to fungi are not extensively studied. Here, we describe interactions of C. elegans and Penicillium brevicompactum, an ecologically relevant mold. Transcriptome studies reveal that co-culture upregulates stress response genes, including xenobiotic-metabolizing enzymes (XMEs), in C. elegans intestine and AMsh glial cells. The nuclear hormone receptors (NHRs) NHR-45 and NHR-156 are induction regulators, and mutants that cannot induce XMEs in the intestine when exposed to P. brevicompactum experience mitochondrial stress and exhibit developmental defects. Different C. elegans wild isolates harbor sequence polymorphisms in nhr-156, resulting in phenotypic diversity in AMsh glia responses to microbe exposure. We propose that P. brevicompactum mitochondria-targeting mycotoxins are deactivated by intestinal detoxification, allowing tolerance to moldy environments. Our studies support the idea that C. elegans NHRs may be regulated by environmental cues.